It is often necessary to deliver drugs to a particular site within a body. For example, catheters are used to deliver drugs or other agents to lumens or vessels within the cardiovascular system, the urethra, bladder, prostate, rectum and central nervous system, such as the spinal cord.
Thrombosis, the formation of a clot or thrombus in the cardiovascular system from the constituents of blood, is a potentially life threatening condition. Thrombosis can develop in any part of the cardiovascular system, but is most common in veins, particularly the deep veins in the leg. Thrombosis can result from a variety of causes including poor circulation, trauma, prolonged bed rest, or hip surgery, for example. In the arteries, thrombosis can be caused by arteriosclerosis. Thrombosis can develop in cerebral vessels, as well.
If a portion of the thrombus separates and is transported through the cardiovascular system, it can cause an embolism, or blockage of a blood vessel. A thrombus in a deep vein in the leg can cause a pulmonary embolism. A thrombus in a coronary artery can cause myocardial infarcation. Similarly, a thrombus in a cerebral artery can cause cerebral infarction.
During the early development of thrombosis, up to about seven days, the thrombus is soft and can be treated by a variety of techniques. Drug delivery catheters have been used to provide thrombolytic drugs or agents such as urokinase, streptokinase and recombinant tissue type plasminogen activator (rTPA), directly onto and into a thrombus. The FasTracker infusion catheter from Target Therapeutics.RTM., for example, comprises a catheter shaft with a drug delivery lumen extending through the shaft. A drug delivery port is located at the distal end of the shaft. To dissolve a thrombus, the FasTracker can be advanced through the thrombus and then withdrawn back through the thrombus as a thrombolytic drug or agent is delivered into the thrombus. This process can be repeated several times. Such a catheter has several disadvantages. For example, it can be difficult to center within the thrombus. In addition, as the thrombus dissolves, the catheter could be drawn to one portion of the vessel by gravity, preventing even delivery of drug to other portions of the thrombus. A catheter which could apply thrombolytic agents evenly to all portions of a thrombus would be advantageous.
In alternative treatments, a pulse spray of a lytic agent, such as urokinase, has been directed onto soft thrombi to mechanically break up and dissolve them. High pressure water has also been directed onto the thrombus to destroy it. The thrombus can also be broken by a laser or a drill. The broken or dislodged portions of the thrombus may be aspirated through a catheter so that they cannot migrate and obstruct other vessels of the cardiovascular system. Results have been mixed, with some treatments damaging tissue, causing another thrombotic or stenotic process. A surgical procedure may be required to remove the thrombus, as well.
It has been found that the application of lytic agents to a clot under pressure provides improved results over diffusion. Blinc, A., et al., "Dependence of Blood Clot Lysis on the Mode of Transport of Urokinase into the Clot--A Magnetic Resonance Imaging Study In Vitro," Thrombosis and Haemostosis, 65(5) 549-552 (1991). U.S. Ser. No. 08/534,856, filed on Sep. 27, 1995, assigned to the assignee of the present invention, discloses driving a drug or other agent through the thrombus by pressure, withdrawing and filtering the thrombic material and delivered drug, and recycling the drug.
In other cardiovascular applications, various types of agents are being investigated for use in preventing restenosis of an artery after percutaneous transluminal coronary angioplasty (PTCA) or percutaneous transluminal angioplasty (PTA). Heparin, an anticoagulant and inhibitor of arterial smooth muscle proliferation, is one such drug. Dexamethasone may also prevent smooth muscle proliferation. Other drugs and agents are being investigated for efficacy, as well. Such drugs can be delivered before or after the angioplasty procedure. The delivery of lytic agents such as urokinase, streptokinase and recombinant tissue type plasminogen activator (rTPA) to dissolve plaque in arteries and veins is also being investigated.
Because of blood flow through the artery, drugs delivered to the site of an angioplasty procedure, for example, can be rapidly dissipated and removed from the delivery site before they can be absorbed in sufficient quantities to become effective. Catheters have therefore been developed to directly deliver drugs to the desired site and maintain them there. For example, U.S. Pat. No. 5,087,244 to Wolinsky et al., discloses a catheter with a flexible balloon having a plurality of minute openings. The balloon can be inflated by heparin. As the walls of the balloon contacts the arterial wall, the heparin exits the balloon, directly on the walls. The balloon can block the perfusion of blood distal to the delivery site, depriving tissue of needed blood. This limits the amount of time available for drug delivery. The inflation of the balloon can also damage the arterial wall, promoting restenosis. In addition, since the balloon is inflated by the heparin, heparin can leak out before the arterial wall is contacted, wasting the drug. The balloon also needs to be deflated prior to removal or to allow blood flow. The pressure required to deflate the balloon could draw blood into the balloon, preventing further use of the catheter until the blood has been removed.
U.S. Pat. No. 4,824,436, also to Wolinsky, discloses a drug delivery catheter comprising a pair of occlusion balloons for securing the catheter in position and isolating a region of the artery which has been opened by PTCA, and a drug delivery conduit for delivering heparin under pressure into the region isolated by the occlusion balloons. The pressure of the heparin forces the heparin to coat and penetrate the arterial tissue. This configuration presents the similar perfusion problems to those discussed above. The heparin, therefore, is only delivered for 5-60 seconds, which may be inadequate for sufficient absorption.
U.S. Pat. No. 5,336,178 to Kaplan et al., discloses a catheter with drug delivery ribs which are brought into contact with the walls of the body lumen by an inflatable balloon. A series of ports in the catheter shaft can be provided proximal to the balloon to allow for perfusion of blood through the catheter shaft. As above, inflation of the balloon can damage the wall of the lumen.
One commercially available drug delivery product is the DISPATCH.TM. from Scimed. The DISPATCH.TM. includes an inflatable polyurethane coil which provides a path for blood to flow and defines regions proximate the wall of the vessel into which drug is delivered. While apparently allowing for significant perfusion, the device is complex and therefore difficult to use and manufacture. The inflatable coil can also prevent portions of the artery from being exposed to the drug and block perfusion to side branch arteries.
It is known that the velocity of fluid flow through a tube varies across the axial cross-section of the tube. The velocity is maximum at the center of the tube and approaches zero at the walls. In an artery or a vein, blood flow is very slow in the region proximate the walls. If drugs or other agents could be effectively delivered proximate the walls, the blood flow can atraumatically carry the delivered drug or agent over the site of interest. The delivered drug or agent would also not dissipate as rapidly as drug delivered to the center of the vessel. Less drug could then need to be delivered, shortening procedures and decreasing their cost.
U.S. Ser. Nos. 08/483,201, and 08/488,216, now U.S. Pat. No. 5,713,853 filed on Jun. 7, 1995 and assigned to the assignee of the present invention, disclose drug delivery catheters with self-expanding drug delivery portions comprising a plurality of resilient members. A shaft, sleeve or other restraining means compresses the drug delivery portion until the drug delivery portion is proximate the site of interest. The restraining means is then retracted or removed, allowing the drug delivery portion to expand radially to bear against the wall of the vessel. Drugs or other agents can then be delivered through lumens in each member.
Drugs and other agents are delivered to lumens, vessels and cavities in other portions of the body, such as the urethra, bladder, prostate, rectum, bile duct, pancreatic duct and central nervous system, such as along the spinal column, to treat a variety of conditions, as well.